Tetrabutylammonium Fluoride → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

HRID 1048447Notes

Reaction equation

HRID 1048447 reaction equation
[Si]([O:18][CH2:19][C@@H:20]([N:23]1[C@H:28]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[C@@H:27]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)[CH2:26][C@@:25]([CH2:44][C:45]([OH:47])=[O:46])([CH3:43])[C:24]1=[O:48])[CH2:21][CH3:22])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:42][C:38]1[CH:37]=[C:36]([C@@H:27]2[C@@H:28]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[N:23]([C@@H:20]([CH2:21][CH3:22])[CH2:19][OH:18])[C:24](=[O:48])[C@:25]([CH2:44][C:45]([OH:47])=[O:46])([CH3:43])[CH2:26]2)[CH:41]=[CH:40][CH:39]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 601541832-((3R,5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Product 1

HCID 585738762-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To an ice-cooled solution of 370 g (0.53 mmol) of 2-((3R,5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 185, Step F) in THF (15 mL) was added 2.60 mL (2.60 mmol) of a 1 M solution of TBAF in THF. The yellow solution was warmed to rt and stirred for 5 h. At this time 2.60 mL (2.60 mmol) of a 1 M solution of TBAF in THF was added and the reaction was stirred for an additional 20 h. The reaction was partitioned between 1 N HCl and EtOAc (4×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. The residue was purified by reverse phase prep. HPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 40% MeCN in water to 80% MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) provided the title compound as a white solid.

Workup

  1. stirringthe reaction was stirred for an additional 20 h
  2. customThe reaction was partitioned between 1 N HCl and EtOAc (4×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was purified by reverse phase prep
  7. washHPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 40% MeCN in water to 80% MeCN in water over a 30 min period, where both solvents

Sources & evidence

ORD record
ord-c52e52fd5bcc440f94f29a837d979233
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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